1. Field of the Invention
The present invention in general relates to natural fat modulators. More specifically, the present invention relates to novel, bioavailable and safe stilbenoid 3,5-dimethoxy-3,4′-dihydroxystilbene possessing an unexpected enhanced ability to prevent the accumulation of lipids accompanying the terminal differentiation of adipocytes, thereby inhibiting adipogenesis. Useful compositions thereof for anti-obesity and anti-cellulite therapy are also described in the invention. Further the present invention also discloses the enhanced SIRT-1 activation ability of 3,5-dimethoxy-3,4′-dihydroxystilbene and 2,3′,5′,6-tetrahydroxy-trans-stilbene. In addition, the present invention also discloses the enhanced anti-Propionibacterium acnes activity of 3,5-dimethoxy-3,4′-dihydroxystilbenes and compositions thereof.
2. Description of Prior Art
It is reported that dietary resveratrol (3,4′,5-trihydroxy-trans-stilbene) at 50 parts per million suppressed blood serum lipid peroxidase levels in rats and dose-dependently suppressed serum triglyceride levels, VLDL and LDL cholesterol levels [Miura, D.; Miura, Y.; Yagasaki, K. Hypolipidemic action of dietary resveratrol, a phytoalexin in grapes and red wine, in hepatoma-bearing rats. Life Sci. 2003, 73, 1393-400]. Naokatu Arakaki et al reported that treatment of differentiated 3T3-L1 adipocytes with H+-ATP synthase inhibitors (resveratrol; picceatannol) lead to a decrease in cytosolic lipid droplet accumulation.
Rimando et al.; document that pterostilbene (3,5-dimethoxy-4′-hydroxystilbene), a natural analog of resveratrol acts as a PPARα agonist and may be a more effective hypo-lipidemic agent than resveratrol itself [J. Agric. Food Chem. 2005, 53, 3403-3407]. This documentation is further validated by Marudhamuthu Amarnath Sateesh and Leelavinothan Pari, who observed that pterostilbene significantly, lowered levels of triglycerides, phospholipids, free fatty acids and total cholesterol in the serum, liver and kidneys of diabetic rats [Journal of Applied Biomedicine, Volume 5 (2008), No 1).
Similarly, Soon-he-Kim et al. reported (Biochemical and biophysical Research Communications 372 (2008) 108-113) that Vitisin A, a resveratrol tetramer inhibited adipocyte differentiation most effectively among others including resveratrol, stilbesterol, Ampelopsin A, Vitisin B, 3,4′,5-Trimethoxy stilbene, and piceatannol. The study showed that 3,5-dihydroxy-4-methoxystilbene, 3,5-dihydroxy-4-methoxystilbene, 3,5-dihydroxy-4-methylstilbene acetate, resveratrol-3-O-B-D-glucoside, resveratrol-3-O-Glu hexaacetate, resveratrol triacetate, rhaponticin, rhaponticin hexaacetate, rhapontigenin, rhapontigenin triacetate, and e-viniferin had no effect on adipogenesis. This study is important prior art in that fat modulation through adipogenesis inhibition is not a common feature among all stilbenoids. Rather, there seems to be a phenomenon of selectivity operating in stilbenoids to inhibit adipogenesis based on their structure and substituted functional groups. While some stilbenoids better others in inhibiting adipogenesis, there are stilbenoids which totally fail to inhibit adipogenesis also.
Adding to the mounting body of evidence on the selective and variable effect of stilbenes towards fat metabolism/modulation, the present inventors disclose the adipogenesis inhibitory effect of 3,5-dimethoxy-3,4′-dihydroxystilbene. The present inventors have unexpectedly found that the adipogenesis inhibitory potential of the said molecule is 5000 times more effective than resveratrol, thereby finding use in anti-obesity and anti-cellulite therapy. The inventors have also found that the SIRT-1 modulatory effects of 3,5-dimethoxy-3,4′-dihydroxystilbene is far superior to resveratrol and pterostilbene enhancing its value as a nutraceutical agent. The molecule also shows considerable promise as a nutraceutical agent in terms of safety profile and bioavailability. In addition, the said molecule also shows far superior anti-acne activity in terms of its anti-Propionibacterium acnes activity when compared to resveratrol reported for the said activity. Also disclosed as a part of this invention is the enhanced SIRT-1 modulating compound 2,3′,5′,6-tetrahydroxy-trans-stilbene.
The principle objectives of the present invention include:
(a) To disclose a novel, orally bioavailable and safe stilbenoid with an unexpected enhanced ability to inhibit the accumulation of lipids accompanying the terminal differentiation of adipocytes, thereby inhibiting adipogenesis and compositions thereof suitable as cosmeceuticals, nutraceuticals and pharmaceuticals.
(b) To disclose a novel, orally bioavailable and safe enhanced sirtuin modulating stilbenoids and compositions thereof suitable as nutraceuticals and pharmaceuticals.
(c) To disclose novel stilbenoid inhibiting the growth of Propionibacterium acnes in an enhanced manner and compositions thereof suitable as cosmeceuticals.
The present invention fulfills the aforesaid principle objectives and provides further related advantages.